The proposed study includes a radioautographic analysis of the distribution of tetrahydrocannabinols (THCs) within the central nervous system in order to determine whether or not this class of drugs is distributed primarily at cell membrane sites or if the distribution is primarily intracellular. We will perform biochemical studies to determine whether or not the THCs have a primary effect on neurotransmitter mechanisms within the central nervous sytem. We will attempt to relate the distribution and biochemical studies of the THCs to physiological responses in two animal models. The physiological responses will include behavioral response in the dog and hypothermia in the mouse. Neurophysiological studies in cats will be used to verify the hypothesis that the THCs have a dual action on central cardiovascular mechanisms. We have proposed that the THCs act directly upon basal motoneurons to depress sympathetic outflow. In addition, the THCs appear to antagonize inhibitory cardiovascular mechanisms from higher centers. The balance between these two mechanisms will determine whether one observed an initial increase in sympathetic outflow which is caused by antagonism of the inhibitory effects from higher centers upon the basal motoneurons or a decrease in heart rate and blood pressure which may result from a direct action of the THCs upon the basal motoneurons to decrease sympathetic outflow. This study provides an explanation for the reported increases in heart rate and blood pressure observed in man after small doses of the tetrahydrocannabinols. Additional studies are described in which thermosensitive neurons have been localized in several areas of the central nervous system. We wish to characterize the effects of both active and inactive THCs upon these neurons. Finally, we shall attempt to integrate the biochemical and neurophysiological mechanisms studied in the cat.